TB under the sea: A marine sponge microbe provides insights into the evolution of tuberculosis | Doherty Website
Tell a creationists that humans and chimpanzees have 98% of their genomes in common, and they'll tell you this doesn't prove common origins or 'macro-evolution', but show them evidence that two bacteria have evolved from a common ancestor because they have 80% of their genome in common and they'll tell you this doesn't mean they've evolved because they are both still 'bacteria kind'.
So, why doesn't 98% commonality mean humans and chimpanzees are both still 'ape kind'?
But the evidence that the two bacteria, Mycobacterium tuberculosis, and the newly-discovered M. spongiae is compelling, and gives a clue as to the origins of M. tuberculosis, one of the most deadly pathogenic bacteria, possibly from marine origins.
What information do you have on the evolutionary origins of Mycobacterium tuberculosis? Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has a complex evolutionary history shaped by its adaptation to human hosts. Understanding the evolutionary origins of Mtb involves examining its genetic relationships with other mycobacteria, its divergence and spread among human populations, and its adaptations over time.The new species was discovered by chance by researchers at the University of Queensland, Australia, who sent it to the Docherty Institute for identification.
- Genetic and Evolutionary Background:
- Mycobacterium Tuberculosis Complex (MTBC): Mtb is part of the Mycobacterium tuberculosis complex (MTBC), a group of genetically related bacteria that cause tuberculosis in humans and other animals. This complex includes several species such as M. tuberculosis (primarily human pathogen), M. bovis (cattle), M. africanum (humans, mainly in West Africa), and M. microti (voles), among others. All members of the MTBC have remarkably conserved genomes with >99.9% nucleotide identity, indicating a relatively recent common ancestor.
- Relationship with Environmental Mycobacteria: Mtb and other members of the MTBC evolved from environmental mycobacteria, which are free-living organisms found in soil and water. The closest relatives to the MTBC are species like Mycobacterium canettii and other "smooth" tubercle bacilli that are found mainly in East Africa. These strains display more genetic diversity than Mtb and its close relatives, suggesting that they represent an ancestral pool from which MTBC members evolved.
- Hypotheses on the Evolutionary Origin of Mtb:
There are two primary hypotheses regarding the evolutionary origins of M. tuberculosis:
- Recent Evolution Hypothesis: This hypothesis suggests that Mtb emerged relatively recently, around 5,000 to 15,000 years ago. Genetic studies support this view, showing that the MTBC has a low level of genetic diversity, which is consistent with a relatively recent common ancestor. This timeline aligns with the development of agriculture and the domestication of animals, which might have facilitated the spread of Mtb among human populations due to increased population density and human-animal interactions.
- Ancient Origin Hypothesis: This hypothesis proposes that Mtb has a much older origin, potentially hundreds of thousands to millions of years ago. Evidence supporting this idea includes genetic studies showing the co-evolution of Mtb with its human host, as well as the discovery of Mtb DNA in ancient human remains dating back thousands of years. Some researchers propose that Mtb co-evolved with early hominids in Africa before the spread of modern humans.
- Genomic Insights:
- Whole Genome Sequencing: Advances in whole-genome sequencing have helped clarify the evolutionary timeline of Mtb. Comparisons of genomes from different strains of Mtb and other mycobacteria indicate that the common ancestor of Mtb and M. canettii-like mycobacteria likely existed in East Africa. The spread and diversification of Mtb are thought to have followed human migration patterns, as strains of Mtb found in different parts of the world align with human genetic lineages.
- Adaptations to the Human Host: Over time, Mtb has adapted to its human host through various genetic mutations. For example, Mtb has lost some genes present in environmental mycobacteria, which is thought to reflect its adaptation to the human respiratory system and a shift from a free-living to an obligate pathogenic lifestyle.
- Coevolution with Humans:
- Association with Human Migration: Mtb shows a strong geographical association with specific human populations, suggesting a long history of co-evolution. For example, different lineages of Mtb are more prevalent in certain regions, reflecting ancient human migration patterns and suggesting that the bacteria diversified alongside human populations as they spread out of Africa.
- Adaptation to Host Immunity: Mtb has also evolved mechanisms to evade the human immune system, such as the ability to persist in a latent state within host cells. This capacity for long-term persistence likely provided a selective advantage, enabling Mtb to survive and transmit even when active disease is not present.
- Possible Animal Origins:
- Role of Animal Hosts: While M. tuberculosis is primarily a human pathogen, its close relative M. bovis causes TB in cattle and other animals, and there is evidence that cross-species transmission has occurred. Some hypotheses suggest that M. bovis may have been transmitted from cattle to humans following the domestication of cattle, but more recent evidence points to humans-to-cattle transmission as more likely. The high degree of conservation in the genome of Mtb and its relatives indicates that transmission to humans may have occurred early and that Mtb then adapted to the human host environment.
- Archaeological and Paleomicrobiological Evidence:
- Ancient DNA Studies: DNA of Mtb has been detected in ancient human remains, such as those found in Egyptian mummies and prehistoric skeletons, providing direct evidence that TB has affected humans for thousands of years. Some studies have found evidence of TB in human remains dating back to the Neolithic period (around 9,000 years ago).
- Molecular Clock Analysis: Estimates using molecular clock models suggest that the Mtb lineage diverged from other mycobacteria around 70,000 years ago, which would coincide with the early migrations of modern humans out of Africa.
- Conclusions on the Evolution of Mtb:
The evolutionary origins of Mycobacterium tuberculosis are likely complex, involving a combination of ancient roots and more recent adaptations. The bacterium appears to have co-evolved with humans over tens of thousands of years, with its spread and diversification closely tied to human migration and social development. While evidence suggests a relatively recent emergence in its current form, its evolutionary trajectory likely began much earlier, shaped by interactions with various hosts and environmental pressures.
The researcher from the Docherty Institute and Queensland University, together with international colleagues under the leadership of Sacha J. Pidot have just published their findings in the journal PLOS Pathogens and explained it in a Docherty Institute News release:
TB under the sea: A marine sponge microbe provides insights into the evolution of tuberculosis
The surprising discovery of a bacterium in a marine sponge from the Great Barrier Reef with striking similarity to Mycobacterium tuberculosis, the pathogen responsible for tuberculosis (TB), could unlock and inform future TB research and treatment strategies.
TB remains one of the world’s deadliest infectious diseases, yet the origins of M. tuberculosis are still not fully understood.
In a new study published in PLOS Pathogens, research led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) details the newly identified bacterium, Mycobacterium spongiae, found in a marine sponge collected near Cooktown, Queensland.
Often referred to as ‘chemical factories’, marine sponges are a valuable source of bioactive compounds with potent anticancer, antibacterial, antiviral and anti-inflammatory properties. While studying a sponge specimen for its chemical-producing bacteria, researchers at the University of Queensland found a bacterium that puzzled them.
The sample was sent to the Doherty Institute, where the team conducted extensive analyses of the genes, proteins and lipids of M. spongiae. They discovered that it shares 80 per cent of its genetic material with M. tuberculosis, including some key genes associated with the bacteria’s ability to cause disease. However, the researchers found that, unlike M. tuberculosis, M. spongiae does not cause disease in mice, making it non-virulent.
The University of Melbourne’s Dr Sacha Pidot, a Laboratory Head at the Doherty Institute and co-lead author of the paper, said it was an exciting and important find.
We were astounded to discover that this bacterium is a very close relative of M. tuberculosis. This finding provides new insights into the evolution of M. tuberculosis, suggesting that these pathogens may have originated from marine mycobacteria.
Dr Sacha J Pidot, lead author
Department of Microbiology and Immunology
Peter Doherty Institute for Infection and Immunity
University of Melbourne, Melbourne, Australia.
The University of Melbourne’s Professor Tim Stinear, a Laboratory Head at the Doherty Institute and co-lead author of the paper, said that that this new knowledge is an important building block for future research.
While there is more work to be done in this space, this discovery is a valuable piece in the puzzle of understanding how TB came to be such a serious disease. Our findings could help find weak links in M. tuberculosis to inform the development of new strategies such as vaccines to prevent and combat tuberculosis.
Professor Timothy P. Stinear, co-corresponding author
Department of Microbiology and Immunology
Peter Doherty Institute for Infection and Immunity
University of Melbourne, Melbourne, Australia.
Collaboration: Authors who contributed were from Bio21 Institute, University of Queensland, Institute Pasteur, UK Health Security Agency, University of Otago and WEHI.
AbstractWhat creationists now need to explain, although they'll almost certainly use their standard tactic of either ignoring the question or pretending (if it is a pretense) of being too stupid to understand it, is why, if this 80% similarity of genomes is just an example of 'micro-evolution' because these are the same 'kind' of bacteria, an even closer similarity between the genomes of humans and chimpanzees (98%) is not an example of 'micro-evolution' because they are the same 'kind' of ape?
Reconstructing the evolutionary origins of Mycobacterium tuberculosis, the causative agent of human tuberculosis, has helped identify bacterial factors that have led to the tubercle bacillus becoming such a formidable human pathogen. Here we report the discovery and detailed characterization of an exceedingly slow growing mycobacterium that is closely related to M. tuberculosis for which we have proposed the species name Mycobacterium spongiae sp. nov., (strain ID: FSD4b-SM). The bacterium was isolated from a marine sponge, taken from the waters of the Great Barrier Reef in Queensland, Australia. Comparative genomics revealed that, after the opportunistic human pathogen Mycobacterium decipiens, M. spongiae is the most closely related species to the M. tuberculosis complex reported to date, with 80% shared average nucleotide identity and extensive conservation of key M. tuberculosis virulence factors, including intact ESX secretion systems and associated effectors. Proteomic and lipidomic analyses showed that these conserved systems are functional in FSD4b-SM, but that it also produces cell wall lipids not previously reported in mycobacteria. We investigated the virulence potential of FSD4b-SM in mice and found that, while the bacteria persist in lungs for 56 days after intranasal infection, no overt pathology was detected. The similarities with M. tuberculosis, together with its lack of virulence, motivated us to investigate the potential of FSD4b-SM as a vaccine strain and as a genetic donor of the ESX-1 genetic locus to improve BCG immunogenicity. However, neither of these approaches resulted in superior protection against M. tuberculosis challenge compared to BCG vaccination alone. The discovery of M. spongiae adds to our understanding of the emergence of the M. tuberculosis complex and it will be another useful resource to refine our understanding of the factors that shaped the evolution and pathogenesis of M. tuberculosis.
Author summary
Tuberculosis, caused by Mycobacterium tuberculosis, is still one of the world’s deadliest infectious diseases. However, the origins and rise of M. tuberculosis as a successful pathogen are not well understood. Here, we report the isolation and characterisation of a marine sponge-derived mycobacterium (M. spongiae) from the Great Barrier Reef that has striking genotypic similarity to M. tuberculosis, with 80% average nucleotide identity. We further show by proteomic and lipidomic analyses that M. spongiae shares virulence factors and unique cell wall lipids with the tubercle bacillus. In spite of these conserved genotypic and phenotypic features, M. spongiae was not virulent in a mouse model of infection, leading us to investigate its potential as a vaccine strain or genetic donor for enhancing the current BCG vaccine for tuberculosis. Our findings contribute to understanding the evolutionary origins of M. tuberculosis and provide further insights into its pathogenesis.
Introduction
M. tuberculosis, the causative agent of human tuberculosis (TB), is the leading bacterial cause of mortality and morbidity worldwide and is responsible for approximately 1.5 million deaths per year [1]. Tuberculosis has affected humans since at least the neolithic expansion of humans across the continents. Despite the wealth of molecular evidence explaining the evolution of mycobacteria that cause tuberculosis in humans and other mammals (the Mycobacterium canettii clade and M. tuberculosis complex, MTBC), the origins of this complex and their differentiation from other mycobacteria are only beginning to be understood.
Several environmental mycobacteria have also been noted as close ancestors of the MTBC, including Mycobacterium marinum, a fish and human pathogen [2], and Mycobacterium kansasii [3], although neither of these mycobacteria have been seen to transmit between humans and they have significantly larger genomes than M. tuberculosis. Recent genomic analyses have identified some other opportunistic human pathogens, such as Mycobacterium riyhadense, Mycobacterium lacus, Mycobacterium shinjukense and Mycobacterium decipiens, that share many features of host-adaptation with M. tuberculosis [4]. However, these closely related, slow growing non-tuberculous mycobacteria (NTM) bacteria differ in many aspects from tuberculosis-causing mycobacteria. These studies suggest that there are likely other taxa to discover that can aid our understanding of M. tuberculosis evolution from a generalist mycobacterium into a highly virulent, specialist human pathogen
Marine sponges are known to house a large and diverse repertoire of bacteria, as attested by recent efforts to catalogue the microbiome of these animals from around the world [5–7]. These studies have shown that Actinobacteria are one of the largest phyla within these microbial communities. As part of efforts to identify and catalogue Actinobacterial symbionts from marine sponges on the Great Barrier Reef in Australia, and to identify possible target species of anti-mycobacterial rifamycins produced by Salinospora sponge symbionts, a mycobacterial isolate named FSD4b-SM was isolated from a Fascaplysinopsis reticulata sponge at a depth of 25m [8]. Initial investigations of this strain showed that it was closely related to the MTBC by conserved gene amplicon sequencing [8].
Here, we sought to better understand the genetic and functional relationships between FSD4b-SM and the MTBC through genomic, proteomic and lipidomic analyses. Our research establishes FSD4b-SM as the most closely related marine organism to the MTBC, assesses its virulence potential, and its prospects for use in TB vaccine development.
[…]
Conclusion
M. tuberculosis and the MTBC have co-existed with humans for millennia. Our knowledge of the evolutionary trajectory that transformed an environmental mycobacterium into a host-adapted mammalian pathogen is enriched every time a new mycobacterium related to the MTBC is discovered [2–4,91–94]. Genomic reconstructions indicate M. tuberculosis evolved from a common ancestor shared with several aquatic environment-associated mycobacteria, including M. marinum, M. kansasii and M. lacus [2,3]. Here we have shown that a mycobacterium isolated from a marine sponge, for which we have proposed the name Mycobacterium spongiae sp. nov. (“of the sponge”), occupies a phylogenetic position even closer to M. tuberculosis than these other mycobacteria, thus adding further support to the hypothesis that the MTBC might have evolved from a marine mycobacterium. It is also interesting to consider that while sponges are not like humans, human lungs are somewhat like sponges at both a gross mechano-anatomical level (they are both biological filters) and also perhaps more profoundly at a molecular evolutionary level, as exemplified by the discovery of a conserved TNF-driven fibrinogenic response to silica exposure in sponges, present also in mammals where it can lead to silicosis [95]. We don’t yet know anything of the interaction between M. spongiae, the host sponge from which it was isolated, Fascaplysinopsis reticulata, and its holobiont. Such interactions will be interesting to observe.
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